Abstract:

Background: In preparation for the Alzheimer’s Prevention Initiative’s (API) first pre-symptomatic Alzheimer’s disease (AD) treatment trial, and in an effort to characterize and compare the trajectory of biomarker changes associated with the preclinical course of AD, we have been conducting cerebrospinal fluid and plasma biomarker, magnetic resonance imaging, as well as fluorodeoxyglucose and florbetapir positron emission tomography (PET) studies in members of the world’s largest known autosomal dominant early-onset AD (EOAD) kindred. Located in Antioquia, Colombia, this kindred includes about,000 living members, approximately0% of whom have a presinilin1 (PS1 E280A) mutation that causes EOAD with a median age of4 at clinical onset. Here, we report preliminary findings from our florbetapir PET studies.
Methods: Fifty family members from Colombia were flown to Phoenix, AZ between September and December,011, for florbetapir PET imaging. Here we report cerebral-to-pontine standardized uptake value ratio (SUVR) from this cohort, including1 symptomatic carriers (7 with MCI, with AD dementia) cognitively normal5-50 year-old adults (9 carriers), and0 cognitively normal8-34 year-old adults (10 carriers).
Results: Compared to non-carriers, patterns of fibrillar amyloid accumulation in both symptomatic and cognitively normal adult PS1 E280A mutation carriers are similar to that found in late-onset AD, characterized by significantly greater florbetapir SUVRs in both cortical and striatal regions. Mean cortical amyloid appears to increase after age0 and plateau in early symptomatic disease. Striatal florbetapir PET binding is seen early, but not prior to mean cortical or other AD-associated regions.
Conclusions: Florbetapir PET findings in this kindred promise to help inform our understanding of pre-symptomatic AD and the performance of these measures in pre-symptomatic EOAD trials.